Immunotherapy with or without chemo has improved survival vs chemo in 1L aNSCLC. NIVO + chemo showed encouraging activity in a phase 1 study in this setting. CheckMate 227 is a multi-part, randomized, open-label, phase 3 study evaluating NIVO-based regimens vs chemo. We present final results from Part 2, which evaluated NIVO + chemo vs chemo in 1L aNSCLC.
Pts (N = 755) with chemo-naive, stage IV or recurrent NSCLC, ECOG PS 0–1, and no sensitizing EGFR/ALK alterations were randomized 1:1 to receive every 3 weeks NIVO 360 mg + chemo or chemo. Pts were stratified by histology (squamous [SQ] vs nonsquamous [NSQ]), sex, and PD-L1 expression (< 1% vs ≥ 1%). Chemo was histology-based and continued for up to 4 cycles; pts with NSQ NSCLC could receive pemetrexed maintenance. Pts were treated until progression, unacceptable toxicity, or for 2 years for NIVO. The primary endpoint was overall survival (OS) with NIVO + chemo vs chemo in NSQ NSCLC. OS in all randomized pts (NSQ and SQ) was a secondary hierarchical endpoint.
Baseline characteristics were generally balanced. Minimum follow-up was 19.5 mo. In pts with NSQ NSCLC, no statistically significant improvement in OS was seen with NIVO + chemo vs chemo (HR, 0.86 [95.62% CI, 0.69–1.08; P = 0.1859]); median OS was 18.8 mo vs 15.6 mo; 12-mo OS rates were 67.3% vs 59.2%. HR for OS was 0.81 (95% CI, 0.67–0.97) in all randomized pts; 0.69 (95% CI, 0.50–0.97) in pts with SQ NSCLC. Progression-free survival and objective response rates favored NIVO + chemo in NSQ, SQ, and all randomized pts (Table). Grade 3–4 tx-related adverse events occurred in 45% and 35% of all pts treated with NIVO + chemo and chemo, respectively.
[Note: Table emailed to Federica Frigerio]
CheckMate 227 Part 2 did not meet the primary endpoint of OS for NIVO + chemo vs chemo in NSQ NSCLC. Descriptive analyses showed longer OS with NIVO + chemo in all randomized pts and SQ NSCLC. No new safety signals were observed.
NCT02477826; Release date: June 23, 2015
Writing and editorial assistance was provided by Namiko Abe, PhD, of Caudex, funded by Bristol-Myers Squibb.